A pressing need in neuro-imaging research towards improved diagnosis and therapies is a practical, high- resolution, quantitative functional imaging tool. To this end we propose to investigate and develop novel methods to support development of high performance, low cost detector designs for PET brain only imaging systems. With the NIH's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative, we believe that human brain imaging will be the largest growth area for PET instrumentation in the near future. The key to enabling the expansion of this technology is to make it lower cost and easy to use such that local clinics can afford to purchase and operate these systems. We introduce the concept of position sensitive sparse sensor (PS3) arrays to facilitate low cost, high performance designs. Our PS3 arrays will be made using silicon photomultiplier (SiPM) devices and custom designed light guides. SiPMs are Geiger-mode avalanche photodiode (GM-APD) devices that have very attractive performance characteristics for PET detectors. They have signal gain similar to photomultiplier tubes (PMTs) and timing characteristics equivalent to or better than PMTs. In addition, they are very compact and can operate in magnetic field environments. However, cost is still a drawback. Using our PS3 concept, we seek to reduce the cost of SiPMs for PET detector designs by greater than 75% while still providing excellent performance for neuroPET imaging applications. To further enable a low cost design, our light guides will use subsurface laser engraving to direct light for enhanced decoding performance. Finally we will enable depth of interaction positioning capability using dual sided (DS) readout and our PS3 arrays. This project consists of two specific aims. We will first investigate via simulation the performance characteristics of different DS-PS3 detector configurations. We will investigate designs using both LYSO and BGO scintillator material. Next, we will develop and fully characterize prototype detector modules. The net result of this work will be the development and characterization of a new low cost PET detector design that will provide outstanding imaging performance for human brain imaging. The long term goal of this work is to develop a low-cost, high performance, brain only positron emission tomography (PET) system with optimized image reconstruction and data processing algorithms. The system will be designed for in office use and/or as a grouped network for drug development or clinical trials testing.